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Detailed information of HUNTINGTON'S DISEASE (WESTPHAL VARIANT)
- incidence: 5-10/100,000 (prevalance)
- age of onset:
- of patients with Huntingon's Disease
- 10% have onset of symptoms prior to 20 years of age
- 5% have onset of symptoms prior to 14 years of age
- 1% have onset of symptoms prior to 10 years of age
- risk factors:
- familial - autosomal dominant
- father is affected in 83% of cases
- chrom.#: 4p16.3
- gene: Huntington Disease (HD) gene
PATHOGENESIS:
- Huntington's Disease belongs to an expanding family of
disorders where the genetic mutation involves unstable
trinucleotide repeats (C_G):
- in this family of disorders, the number of repeats tends
to increase with succeeding generations ("genetic
anticipation")
- in Huntington's Disease:
- the HD gene was isolated by James Gusella's group in
winter of 1993 and an unstable part of the gene was
identified in the coding region characterized by numerous
repeats of single trinucleotide sequences containing the
bases cytosine, adenine, and guanine (CAG)
- in normal individuals, there are between 9-34 CAG
repeats but in those with HD, there may be between 30-100
CAG repeats
- the function the the HD gene product is unknown
2. Genetic Defect
- genetic defect -> amplification of the sequence of
unstable trinucleotide repeats (CAG) to greater than 30 ->
encodes a long tract of glutamine residues -> altered protein
-> pheno-typic expression of the disease
- there is a strong inverse correlation between the length
of the CAG repeat and the age of onset of the disease
CLINICAL FEATURES:
- initially presents with bradykinesia and rigidity
- may also initially present with behavioural or cognitive
deterioration and poor school performance
2. Late
- chorea tends to involve proximal muscle groups
- associated features
- 50% - generalized tonic-clonic seizures
- 50% - cerebellar signs
- 20% - oculomotor apraxia
- gait disturbances
- more rapid course in children than in adults
- average of 8 years till death (14 years in adults)
INVESTIGATIONS:
- identification of amplified CAG sequences in the HD gene
of affected individuals
2. Imaging Studies
- atrophy of the caudate nucleus and frontal cortex
- dilatation of the lateral ventricles
MANAGEMENT:
- movement disorders
- bradykinesia/rigidity - antiparkinsonian drugs
- chorea - dopamine antagonists
- behavioural problems
- neuroleptics and/or antidepressants
- seizure disorder
- very resistant to anticonvulsant therapy
2. Supportive
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Pediatric Database - HUNTINGTON'S DISEASE (WESTPHAL VARIANT)
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